26 Mar 2005

Randomized Phase I study limited to 48 patients to determine safety -

Researchers at Johns Hopkins have begun what is believed to be the first clinical trial in the United States of adult mesenchymal stem cells to repair muscle damaged by heart attack, or myocardial infarct.

The so-called Phase I study is designed to test the safety of injecting adult stem cells at varying doses in patients who have recently suffered a heart attack.

An estimated 7 million Americans alive today have suffered at least one heart attack and so are at greater risk for chronic heart failure, sudden cardiac death or another, potentially fatal, heart attack.

"This is an important milestone on the journey to better cardiovascular care and to realization of the promise of adult stem cell research," says lead study investigator and cardiologist Joshua Hare, M.D., professor of medicine at The Johns Hopkins University School of Medicine and its Heart Institute.

"Current approaches to cardiovascular disease can prevent heart attack or alleviate its after-effects, but they have not included repair of damage that leaves sizably dead portions of heart tissue as dangerous scars in the heart," says study co-investigator and cardiologist Steven Schulman, M.D., a professor at Hopkins and director of the coronary care unit at The Johns Hopkins Hospital.

Previous research in animals showed that when adult stem cells were injected directly into the heart muscle, heart function was restored to its original condition within two months. Last November, at the American Heart Association Scientific Sessions 2004, the Hopkins team showed, again in animal studies, that more than 75 percent of dead scar tissue disappeared after therapy, which produced mostly healthy, normal-looking heart tissue and left only a small trace of the heart attack.

The Phase I study is being conducted at Hopkins, with support from Baltimore-based Osiris Therapeutics, which developed the stem cell product. The study will involve 48 adults who have had their first heart attack within 10 days of enrollment in the trial. All patients will have been stabilized before acceptance to the trial, and have undergone cardiac catheterization and ultrasound echocardiography to check that their main coronary vessels are clear of blockages that may precipitate another heart attack.

Eligible candidates must be able to safely travel to Hopkins Hospital in Baltimore, Md., be referred by a physician, be between 21 and 85 years old, and have no pre-existing heart condition that has been treated or requires treatment during the study period. Physicians interested in referring patients should call tel. 410-955-1160 for further information.

Upon acceptance in the study, patients will be randomly assigned to one of four groups, each made up of 12 patients who will receive a preset dose of stem cell therapy or placebo. The study is double blinded, with neither researchers nor patients aware of who received stem cells until the Phase I study ends, six months after the last patient has enrolled.

After injecting stem cells taken from the bone marrow of an adult, human donor, into subjects' bloodstream, the researchers will monitor the patient's progress for two years to ensure that patients safely tolerated the infusion, determine any side effects and assess any differences in the three doses under study, each involving millions of adult stem cells. Initially, study participants will spend four days in the hospital, immediately after the procedure. The patients will then return for preset checkups, monthly for the first three months, and again after six months, 18 months and 24 months.

Magnetic resonance imaging (MRI) studies, to show the size of the area of heart muscle scarred by the infarct and gauge the organ's ability to pump, will be conducted at the beginning and end of the study as a measure of heart function. Conclusive results will only be available when and if Phase II and Phase III clinical trials proceed.

The Hopkins team expects that after injection, the adult stem cells will migrate to the damaged areas of the heart muscle, responding to chemical signals released by the heart after an infarct that triggers a repair response from the bone marrow.

Related clinical research under way in China also uses adult stem cells, but they come directly from the patient, and no universal donor is used as in the Hopkins study.

It remains unclear from earlier animal studies how or why the adult stem cells develop into new and healthy heart tissue, or exactly how long their healing effects last.

Adult stem cells are being used because they are readily available from the bone marrow, where they are plentiful. A special kind of bone marrow stem cell, called a mesenchymal stem cell, was separated from other kinds for use in this study. While their precise biological action is not known, mesenchymal bone marrrow stem cells are known to give rise to a variety of cell types, including bone, cartilage, fat, and other kinds of connective tissue cells such as those in tendons, as well as muscle, such as the heart. A stem cell is a special type of body cell that gives rise to other types of specialized cells.

"Using mesenchymal stem cells also avoids potential problems with immunosuppression, in which every human's immune system might attack stem cells from sources other than itself," notes Hare. "Because they remain in an early stage of development, mesenchymal stem cells do not trigger an immune response, unlike what would happen if more developed stem cells were used.

"While the bone marrow adult stem cells do not have the same potential to develop into different organ tissues as do embryonic stem cells, the use of adult stem cells in this study shows their tremendous potential in developing effective therapies for heart disease, and avoids the controversy surrounding destruction of embryos to obtain the embryonic variety," he adds.

"Among its many benefits are that adult stem cells are readily available from a number of donors, and grow in large quantities in the lab. In our experiment, the treatment regimen is relatively simple, requiring only injection."

Funding for the study is provided by Osiris Therapeutics, which developed the process for preparing the adult mesenchymal stem cell product in use in the study. Additional funding comes from Hopkins' General Clinical Research Center, its Institute for Cell Engineering, and the Donald W. Reynolds Cardiovascular Clinical Research Center at Johns Hopkins. Other investigators in this research are Stuart Russell, M.D.; Ilan Wittstein, M.D.; Gary Gerstenblith, M.D.; Alan Heldman, M.D.; João Lima, M.D.; and Kathy Wu, M.D.

According to the latest statistics from the American Heart Association, in 2002, there were an estimated 565,000 new cases of heart attack in the United States, plus an additional 300,000 cases of recurrent heart attack. Almost 180,000 of all heart attacks were fatal. The AHA also estimated that 7,100,000 Americans had suffered at least one heart attack. People who have had a heart attack have a sudden death rate that is four to six times greater than in the general population. About two-thirds of heart attack patients do not make a complete recovery; however, 88 percent of those under age 65 are able to return to work.

Study Inclusion Criteria:
hopkinsmedicine.org/Press_releases/2005/StudyInclusionCriteria.html

Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
http://www.hopkinsmedicine.org

http://www.medicalnewstoday.com/medicalnews.php?newsid=21829

UConn Said Close to Creating Stem Cells

Fri Mar 25, 9:11 PM ET

STORRS, Conn. - As lawmakers consider plans to make the state a hotbed for stem cell research, the University of Connecticut has announced it is poised to become one of the first colleges in the country to launch a program for making human embryonic stem cells.

Xiangzhong "Jerry" Yang, a cloning expert who directs UConn's Center for Regenerative Biology, said Thursday that his laboratory had become the first to create embryonic stem cells from cloned cattle embryos. The work was done in a partnership with the Institute of Zoology of the Chinese Academy of Sciences.

Yang said the lab is ready to move from studying stem cells in cows to creating human embryonic cells for research, but he said China is asking him to do the work in Beijing.

Although he does not plan to leave UConn, Yang said he or other scientists at the Center for Regenerative Biology would consider moving their work to China if the state does not pass a bill supporting stem cell research.

Researchers at Yale University Medical School are also concerned about having enough money to study stem cells. School officials say they are ready to create a new stem cell institute, but are worried about competition from other states such as New Jersey and California, which plan to spend billions of dollars on research.

Scientists worldwide are eager to dive into the field because certain stem cells can morph into all cell types found in the body. Some scientists believe that stem cells can be used to repair damaged tissue, replace entire organs and cure diseases such as diabetes, Parkinson's and Alzheimer's.

UConn's results with cloned cattle embryos are published in the current issue of the journal Biology of Reproduction.

Yang said developing a therapeutic cloning program to make human embryonic stem cells will need the backing of Connecticut lawmakers. The U.S. government has prohibited federal funding on human embryonic cells created after the fall of 2001.

Embryonic stem cells so far have been created only from cloned embryos in mice and in humans.

In his research, Yang plans to implant DNA from a skin cell into an egg that has had its own DNA removed. The egg is electrically stimulated and begins cell division. Within five days, the new embryo creates an interior ball of embryonic stem cells.

Yang envisions therapeutic testing beginning within the next 10 years.

State Sen. Christopher Murphy, D-Cheshire, co-chairman of the legislature's Public Health Committee, said now is a critical time in the stem cell movement for recruiting scientists. He supports a bill that would provide $10 million in bonding for stem cell research in the coming year and ban cloning designed to produce a child.

Opponents of the plan, including officials of the Roman Catholic Church, argue that there are not enough safeguards that prevent scientists from creating a human being from a cloned embryo. They also believe the embryos are alive and should not be killed in order to promote research.

Dr. Robert Alpern, new dean of the Yale School of Medicine, said Thursday that Yale wants to create a new stem cell center that would bring six or seven top-flight scientists together.

To attract and keep top researchers, he said, the center would require lab space and ongoing funding for stem cell research that currently is ineligible for federal grants.

Fifteen other states are considering bills similar to the measure before the Connecticut legislature, said Paul Pescatello, president of Connecticut United for Research Excellence, which supports the legislation.

"People are being wooed, and they are waiting to see what happens with this legislation and how much money comes to bear on their labs," Pescatello said.

Information: The Hartford Courant, http://www.courant.com.

Plans $10M for Stem Cell Research

By MAURA KELLY LANNAN, Associated Press Writer
Wed Jul 13, 6:14 AM ET





CHICAGO - Illinois became the fourth state to support stem cell research after Gov. Rod Blagojevich circumvented the Legislature and ordered $10 million in tax dollars be used for the controversial research.

Blagojevich's executive order earmarks grants to medical research facilities for research on adult, cord blood and embryonic stem cells and is not to be used for reproductive cloning.

"My sense of morality argues strongly to not simply sit back and do nothing when children are suffering from juvenile diabetes," said Blagojevich, a Democrat. "To simply be afraid to take a position or to act, I think would be immoral."

Lawmakers, who have questioned whether state funds should be used for research in such an ethically sensitive area, have debated related measures twice in the past year and either rejected state support outright or shelved the idea without a vote.

The Illinois program will use money from the state's general budget. California, Connecticut and New Jersey also provide state funding for stem cell research.

The Bush administration has withheld federal funding for the practice. The U.S. House passed and the Senate is now considering legislation that would loosen Bush's 2001 restrictions on federal money for new human embryonic stem cell studies.

Scientists say the study of stem cells, which can divide and become any kind of cell in the body, could lead to cures for diseases such as diabetes and Alzheimer's.

Opponents of stem cell research believe it is immoral because it destroys an embryo, which many consider to be human life.

Robert Gilligan, executive director of the Catholic Conference of Illinois — the public policy arm of the state's Catholic bishops — questioned Blagojevich's move.

"I think it's shameful. I think it's a disgrace that, on July 12, when the Legislature is not in session, he finds $10 million dollars to partially fund something that's morally objectionable to many people," Gilligan said.

Opponents also blasted the governor for ignoring lawmakers and hiding money in the budget. Senate Republican Leader Frank Watson said he did not know the budget contained money for stem cell research.

"If it includes embryonic, that's an end-run of the Legislature. I don't know if he has the authority to do it," Watson said.

Gretchen Livingston, legislative chairwoman for the Chicago chapter of the Juvenile Diabetes Research Foundation, said the move might help find a cure for her daughter's diabetes.

"I'm not content to wait while politics cloud the science and interfere with real progress toward cures," she said.

http://news.yahoo.com/s/ap/20050713/ap_on_he_me/stem_cell_research

Studies Show New Ways to Get Stem Cells

By MALCOLM RITTER, AP Science Writer
39 minutes ago

NEW YORK - Two new mouse experiments may show how to obtain human embryonic stem cells without ethical hurdles, a step that could allow federal funding for such research, scientists reported Sunday.

Currently, scientists must sacrifice human embryos to harvest such cells, which can form any tissue type and are seen as valuable for studying and treating illnesses like diabetes and Parkinson's disease.

Objections to the embryo destruction have led to a ban on federal funding for such work, which scientists say hampers research.

The new methods, detailed Sunday in the online edition of the journal Nature, seek to obtain the cells without destroying embryos.

The Coalition for the Advancement of Medical Research, which advocates federal funding of stem cell research, cautioned that despite the goal of avoiding ethical quandaries, the new approaches "will not sit well with many who oppose embryonic stem cell research."

An official with the U.S. Conference of Catholic Bishops said the two reported techniques still raise ethical objections, although a spokesman for a group of Roman Catholic bioethicists called one of them a step in the right direction.

In the standard method of harvesting stem cells, researchers wait five days or so after fertilization until the embryo has become a ball of up to 150 cells. They obtain stem cells from the interior of the ball, which destroys the embryo.

One of the new mouse studies borrowed a lab technique used in fertility clinics, called pre-implantation genetic diagnosis or PGD. It is used to screen embryos for genetic disorders.

In the study, researchers plucked a single cell from eight-cell mouse embryos, which were about two days old. While fertility clinics use such a cell for genetic testing, the researchers cultured the plucked cells and found they behaved like embryonic stem cells. The embryos, meanwhile, went on to produce mice.

The result suggests that when clinics do PGD, they could let the cell they remove divide into two, and use one resulting cell for genetic testing and the other to establish a stem cell line, said Robert Lanza of Advanced Cell Technology in Worcester, Mass., an author of the study.

But Richard Doerflinger, deputy director of pro-life activities for the Catholic bishops conference, said PGD itself is unethical. It poses a risk of harm and is mostly an effort "to select out genetically imperfect embryos," he said.

The second mouse study used a modified form of therapeutic cloning, a technique that aims to generate stem cells that genetically match a patient, for either treatment or research.

Results were reported by Dr. Rudolf Jaenisch and Alexander Meissner of the Whitehead Institute for Biomedical Research and the Massachusetts Institute of Technology in Cambridge, Mass.

As with normal therapeutic cloning, they took eggs whose DNA-containing nuclei had been removed and inserted in each one a nucleus from a body cell of a mouse. But before the insertion, they blocked the action of a key gene in the nuclei, to ensure the eggs could not produce an embryo that can implant in a uterus. Yet, the eggs divided and grew enough to yield stem cells.

This modified technique, called altered nuclear transfer, has been championed by Dr. William Hurlbut of Stanford University, a member of the President's Council on Bioethics. He said the abstract cluster of cells the egg produces is not an embryo but a "non-embryonic entity" that lacks an embryo's developmental potential.

"You don't create a living being," he said.

Doerflinger disagreed, saying the technique appears to create and then destroy an embryo, which would make it unethical.

But the Rev. Tad Pacholczyk, director of education for the National Catholic Bioethics Center in Philadelphia, called the approach a step in the right direction. Scientists are already discussing a modified version in which adding the nucleus to the egg would result in a single stem cell, not an embryo, he said.

Seen in that light, he said, the mouse study "is very encouraging. It reminds us that we have certain tools at our disposal in the scientific armamentarium that can be used in the direction of seeking an answer to the ethical impasse."

___

On the Net:

Nature: http://www.nature.com/nature

Advanced Cell Technology: http://www.advancedcell.com

Jaenisch background: http://www.wi.mit.edu/research/faculty/jaenisch.html

National Catholic Bioethics Center: http://www.ncbcenter.org

AP - Fri Oct 7, 5:37 PM ET
In this photo released today from Childrens Hospital Los Angeles, French stem cell scientist Dr. Alain Fischer, one of the world's foremost authorities on immunodeficiencies in children, shares his findings on his stem cell research with scientists and physicians at The Saban Research Institute of Childrens Hospital Los Angeles, Friday, Oct.7, 2005. Fischer, from Paris, has pioneered understanding, diagnosis and treatment for critically ill infants with severe combined immune deficiency disease. His clinical program was part of several French and European clinical trials using hematopoietic stem cell transplantation. (AP photo/Childrens Hospital Los Angeles, Bob Riha, Jr.)

http://news.yahoo.com/s/ap/20051016/ap_on_he_me/stem_cells

Australian Stem Cell Discovery Could Help Fight Breast Cancer

By Claudia Blume
Hong Kong
05 January 2006

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Scientists in Australia have discovered a stem cell that is expected to provide clues about how breast cancer develops, and how cancer cells evade current therapies. The discovery could be a breakthrough in the treatment of breast cancer.

Researchers at the Victorian Breast Cancer Consortium in the Australian city of Melbourne say they have discovered the stem cell that controls the formation of breast tissue.

Stem cells are the basic building blocks of all body parts, from muscles to blood vessels to nerves.

The Australians isolated these newly identified stem cells from the breasts of female mice.

Under normal circumstances, this type of stem cell produces healthy breast tissue. But a genetic predisposition to cancer, or exposure to carcinogens (cancer-causing agents), can cause a particular cell to grow into a cancerous tumor.

The existence of these "rogue" stem cells could explain why some women begin developing breast tumors again following chemotherapy - a development that has puzzled scientists and doctors for many years.

Chemotherapy is most effective at destroying cancer cells that divide rapidly. But the newly found stem cell divides slowly: it can survive for months or even years after chemotherapy, and then break out into a new cancer.

The leader of the Australian research team, Jane Visvader, says the main goal of her team is to understand how these stem cells work, and then find a drug that will stop them from becoming malignant.

"The main goal is to understand the nature of both the normal stem cells and the stem cells that become aberrant and accumulate errors and therefore, use this information to try and design drugs to target these cells," she said.

Ms. Visvader says it could take 10 to 20 years to develop such a drug. In the next step of the research, tumor samples from human breast cancer patients will be analyzed to confirm the findings of the mouse model.

Ms. Visvader says the research team was also able to grow fully functional breasts in mice from the stem cells. But she says that growing new breasts in human patients to replace breasts removed because of cancer is only a remote possibility.

"And that is because mice and [human] breast tissue differ quite significantly in their make-up," she explained. "The hormones and growth factors that are likely to be involved in regenerating the breast will also be involved in the tumor-genic process that is leading cells to become cancerous."

In other words, the same factors that might cause a new breast to grow might also cause a new cancer.

The findings of the Australian researchers, published in the scientific journal Nature this week, have been corroborated by a Canadian research team.

http://www.voanews.com/english/2006-01-05-voa20.cfm

Muscle Stem Cells Transformed Into Cartilage

By Ed Edelson
HealthDay Reporter
Mon Jan 30, 5:02 PM ET

MONDAY, Jan. 30 (HealthDay News) -- Researchers say they have turned adult muscle stem cells into cartilage, and used them in animals to heal the kind of damage caused by arthritis.

That is potentially good news for the many people who now face joint-replacement surgery because there is no available technique to repair cartilage damage from osteoarthritis, the wear-and-tear condition that afflicts many older people.


The transformed cells have successfully replaced damaged cartilage in rats for as long as 24 weeks, much longer than has been reported in studies using other methods, according to a report in the February issue of Arthritis & Rheumatism.


Experiments aimed at extending the benefit to 48 weeks are in the planning stage, with an eye out for human trials, said study leader Johnny Huard, director of the Growth and Development Laboratory at the Children's Hospital of Pittsburgh.


"Over the years, a lot of people have tried to use cells to repair cartilage, which doesn't repair by itself," said Huard. "So far, nobody has been able to repair cartilage with those cells. In this study, we found a population of stem cells in skeletal muscle that we give a boost with a protein so they differentiate into cartilage cells. Then we can repair cartilage damage in our animal model."


Discovery of the protein that does the transformation was one of those happy accidents, Huard added. It is bone morphogenetic protein-4 (BMP-4), so named because it has been used for years to make bone cells. A look at the cells thus treated in a different project showed they resembled cartilage cells, and that observation led to the new breed of cartilage cells.


If all works out as hoped, Huard said, treatment of damaged cartilage would start with a biopsy to obtain muscle stem cells from the person needing the treatment. "That is the nice thing about it, because by taking muscle cells from you, we bypass the immune reaction against foreign cells, he said.


The cells would then be grown in culture to create patches for the damaged cartilage.


The experiments described in the journal report used 36 young rats, all with damaged cartilage, who were divided into three groups. One of those groups got muscle stem cells genetically engineered to produce BMP-4, another got plain muscle stem cells, the third just got a coating of glue. Studies over the next 24 weeks showed repair in the BMP-4 mice, and not in the others.


It's not possible to say when human trials of the transformed cells might start, Huard said. But human trials are underway to test the safety of muscle stem cells against a different condition, bladder dysfunction, which causes embarrassing leakage, he said.


An accompanying editorial by Dr. Mary B. Goldring, of the New England Baptist Bone and Joint Institute, said the study "provides proof-of-principle for performing muscle-derived stem cell implantation in cartilage of humans, since 12-week-old rats are considered to be young adults," and that "further work is warranted" to see if the method works in humans.

More information

More on cartilage and what can go wrong with it is available from the National Library of Medicine.


http://news.yahoo.com/s/hsn/20060130/hl_hsn/musclestemcellstransformedintocartilage

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http://vnthuquan.net/diendan/tm.aspx?m=67395&mpage=1&key=&#180567



Bush spokesman Snow apologizes for stem cell remark

Mon Jul 24, 4:11 PM ET

WASHINGTON (Reuters) - Tony Snow, President George W. Bush's chief spokesman, apologized on Monday for saying Bush believed embryonic stem cell research amounted to "murder," saying he had overstated the president's position.

Snow, a former radio talk show host who took over as press secretary in May, created a bit of a stir in defending Bush's veto last Wednesday of legislation that would have expanded embryonic stem cell research.

"The president believes strongly that for the purpose of research it's inappropriate for the federal government to finance something that many people consider murder. He's one of them," Snow had said.

Asked about that comment on Monday, Snow told reporters: "I overstepped my brief there" and said he was sorry the remark became a subject for White House chief of staff Josh Bolten in an appearance on NBC's "Meet the Press" on Sunday.

"I feel bad about it," Snow said.

Bush himself said, in casting the veto, the legislation "crosses a moral boundary."

Asked if Bush considered it murder, Snow said: "He would not use that term."